Over the past four years, Explicyte and Bergonié Institute have been conducting joint translational research programs to identify determinants of cancer patients’ responsiveness to immunotherapy. Among these efforts, Explicyte and a research team led by Pr. Italiano at Bergonié Institute identified a key biomarker predictive of the efficacy of immunotherapy in oncology.
Bordeaux, France, June 12, 2023 – Over the past four years, Explicyte and Bergonié Institute have been conducting joint translational research programs to identify determinants of cancer patients’ responsiveness to immunotherapy. While the latter is a fundamental therapeutic breakthrough for a variety of malignancies, rates of response remain limited and immunotherapy effectiveness can thus be improved. One line of research focused on immune checkpoint inhibitors of the PD-1 / PD-L1 axis (programmed cell death-1 receptor and its ligand), which play a key role in the control of the anti-tumor immune response.
Among these efforts, Explicyte, a CRO specializing in immuno-oncology, and a research team led by Pr. Italiano at Bergonié Institute, identified a key biomarker predictive of the efficacy of immunotherapy in oncology. In two main articles published in Nature Cancer (2021) and Nature Medicine (2022), they highlighted the determining role of mature tertiary lymphoid structures (mTLS). The results obtained support the ambition of making precision medicine a reality.
In a first pioneering study (Vanhersecke et al, Nat Cancer, 2021), the team demonstrated that the presence of mTLS within the tumor is associated with improved objective response rate – progression-free survival and overall survival – in several tumor types. In this work, samples from three independent cohorts of cancer patients treated with PD-1 / PD-L1 axis blockers were investigated by pathologists from Bergonié Institute, relying on Explicyte’s expertise and advanced technological platforms.
These early results provided a strong rationale to design the first biomarker-driven clinical trial evaluating the benefit of Pembrolizumab (a monoclonal antibody directed against PD-1) in patients with sarcomas characterized by the presence of TLS. This second study (Italiano et al, Nat Med, 2022) demonstrated a clear benefit of immunotherapy in this subclass of patients, whereas no benefit was shown in unselected patients (Toulmonde et al, JAMA Oncol, 2018). In addition, Explicyte scientists have further identified regulatory T cells (Tregs), a specific subpopulation of immunosuppressive cells, as limiting the efficacy of immunotherapy in TLS-positive patients.
“The partnership between Bergonié Institute and Explicyte has demonstrated its ability to achieve breakthroughs in the growing field of immuno-oncology. Our joint efforts will continue to support the strong benefit of precision immunotherapy while shedding light on our translational service capabilities”.
Alban BESSEDE, PhD, CEO of Explicyte
“Thanks to our research programs conducted with Explicyte, we are the first to demonstrate the benefit of biomarker-driven immunotherapy for sarcoma patients and we will continue our efforts to prove the benefit of this strategy for all cancer patients. The partnership we established with Explicyte represents a force to move forward with precision immunotherapy and bring significant advances in healthcare to cancer patients”.
Antoine ITALIANO, MD, PhD, Head of Early Phase Trials Unit, Bergonié Institute
References
Vanhersecke, L., Brunet, M., Guégan, JP. et al. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Nat Cancer 2, 794–802 (2021). (link)
Italiano, A., Bessede, A., Pulido, M., et al. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat Med, 28(6), 1199-1206 (2022). (link)
Toulmonde, M., Penel, N., Adam, J., et al. Use of PD-1 targeting, macrophage infiltration, and IDO pathway activation in sarcomas: a phase 2 clinical trial. JAMA Oncol, 4(1), 93-97 (2018).(link)
About Explicyte
Explicyte is a Contract Research Organization whose mission is to support the discovery and development of pioneering therapies in immuno-oncology. To this end, it offers integrated preclinical and translational research services combining state-of-the-art in vitro and in vivo approaches combined with cutting-edge technologies. Its cell-based assays can be used to screen novel immunotherapies and delineate their related mechanisms of action. Relying on well-characterized syngeneic mouse tumor models, its comprehensive in vivo platform enables exploration of the anti-tumor immune response to innovative immunotherapies. At last, its translational services help support projects from the identification to the validation of new targets and biomarkers, relying on extensive analyses covering the tumor and its microenvironment. Besides these activities, Explicyte constantly develops innovative in vitro and in vivo models to best serve its clients’ programs.
About Bergonié Institute
Bergonié Institute is labeled by the French National Cancer Institute as a reference center for early-phase clinical trials (CLIP2) in oncology and a national referral center for the diagnosis and management of patients with sarcomas. Between 2015 and 2018, the Early Phase Clinical Trials unit led by Pr Antoine Italiano enabled more than 3,000 patients with advanced cancer to benefit from an early phase clinical trial, making Bergonié Institute a European leader in the field of therapeutic innovation. The Early Phase Clinical Trials Unit supports industry-sponsored research in patients with all types of solid tumors and hematological cancers.